Polymorphism of genes of hemostasis system and methionine exchange in patients with female reproductive tumors.
Authors: Anna P. Menshenina, Ekaterina V. Verenikina, Tatiana A. Zykova, Elena A. Shevyakova, Meri L. Adamyan, Oksana E. Zhenilo, Yuriy A. Poryvaev, Vera P. Nikitina, Tatiana I. Moiseenko, Elena M. Frantsiyants, Oksana V. Katelnitskaya, Anna Yu Ardzha
Journal: Journal of Clinical Oncology (2022)

e17500 Background: Our purpose was to analyze the rates of polymorphic allelic variants of genes of hemostasis system and methionine exchange in patients with female reproductive tumors. Methods: The study included 51 patients with histologically verified gynecologic tumors (group 1), including 28 patients (group 1a) with malignant tumors (cervical cancer (CC) n = 8, ovarian cancer (OC) n = 8, endometrial cancer (EC) n = 8, other cancers n = 4) and 23 patients (group 1b) with benign tumors, and 47 women without tumors (group 2). 12 polymorphic loci were studied by RT-PCR in genomic DNA samples: F2 (G20210А, rs1799963), F5 (G1691A, rs6025), F7 (G10976A, rs6046), F13 (G226A, rs5985), FGB G(-455)A (rs1800790), ITGA2-α2 (C807T, rs1126643), ITGB3-b (Т1565С, rs5918), PAI-1 4G(-675)5G, rs1799889), MTHFR (С677Т, rs 1801133 and A1298C, rs1801131), MTR (А2756G, rs1805087), MTRR (A66G, rs1801394). Groups 1, 1a and 1b were compared with controls (p 1 ) and among themselves (p 2 ). Results: The ratio of genotype frequencies maintained in the Hardy-Weinberg equilibrium in all gene loci except F7 (G10976A) in group 1 (p = 0.03). An alternative allele in the F2 gene was found only in group 2 (1.1%). The frequency of an alternative allele in the F5 gene in group 1 was 2.9%, including 1a – 1.8%, 1b – 4.3%, group 2 – 2.1%; F7 – 16.7%, 14.3%, 19.6% and 17.0%; F13 – 23.5%, 23.2%, 23.9% and 34%; FGB – 26.5%, 25.0, 28.3% and 25.5%; ITGA2 – 53.9% (p 1 = 0.03, OR = 1.89 (1.07-3.33), 48.2%, 60.9% (p 1 = 0.01, OR = 5.21 (1.22-5.17) and 38.3%; ITGB3 – 13.7%, 10.7%, 17.4% and 16.0%; PAI-1 – 47.1% (p 1 = 0.03, OR = 0.53 (0.30-0.93), 46.4%, 47.8% and 62.8%; MTHFR (Т) – 28.4%, 30.4%, 26.1%, 34.0%; MTHFR (С) – 34.3%, 28.6%, 41.3% (p 1 = 0.04, OR = 2.17 (1.02-4.61) and 24.5%; MTR – 18.6%, 19.6%, 17.4% and 27.7%; MTRR – 63.7%, 71.4%, 54.3% and 62.8%, respectively. TT genotype at the ITGA2-α2 (C807T) locus was more frequent in group 1 than in group 2 (23.5% vs 19.1%, p 1 = 0.01, OR = 6.54 (2.61-16.40); CT genotype was more frequent in group 1a than in group 2 (67.9% vs 38.3%, p 1 = 0.004, OR = 3.40 (1.27-9.13), and more frequent in EC than in group 2 (87.5% vs 38.3%, p 1 = 0.03, OR = 11.28 (1.28-99.40). GG genotype at the MTRR (A66G) locus was more frequent in group 1a than in group 1b (53.6% vs 26.4%, p 2 = 0.042). 5G5G genotype at the PAI-1 4G(-675)5G locus was more frequent in group 1 than in group 2 (31.4% vs 10.6%, p 1 = 0.04, OR = 3.84 (1.28-11.53), and more frequent in OC than in group 2 (75% vs 11%, p 1 = 0.0001, OR = 25.50 (3.96-160.20). AA genotype at the F7 (G10976A) locus was more frequent in CC patients than in group 2 (31.3% vs 17%, p 1 = 0.03, OR = 15.33 (1.20-195.75). Conclusions: Carriage of the AA genotype at the F7 (G10976A) locus may increase the risk of developing CC, and the CT genotype at the ITGA2-α2 (C807T) locus may increase the risk of EC. On the contrary, the alternative 4G allele at the PAI-1 4G(-675)5G locus was less common in patients with malignant tumors, especially OC, than in the group without cancer.